Gene balances sex chromosomes in male birds

A gene has been found to help male birds survive by keeping their sex chromosomes in balance.

The gene is of a type known as a microRNA, which acts like a dimmer switch to lower the activity of other important genes in males. 

When this microRNA was removed from male chicken embryos, the birds failed to develop. 

The results show that birds evolved a unique way to balance gene activity between the sexes, and this differs from the mechanism that resolves the equivalent imbalance in mammals.

The gene helps address an imbalance that derives from male birds having two Z chromosomes, whereas females have one Z and one W – and over millions of years, the W chromosome in females has evolved to lose many of its genes. 

This creates a disproportion – some important genes have two copies in males, but only one copy in females. These genes can’t function properly if there is too little or too much of them. 

A team of researchers, led by Uppsala and Heidelberg Universities and the Roslin Institute, focused on a microRNA on the Z chromosome which is active mainly in male birds. They sought to investigate whether the gene, known as miR-2954, might help balance gene activity. 

To find out, researchers used gene editing to remove this microRNA in chickens. 

The team was struck by the results – all male embryos lacking both copies of the microRNA on their Z chromosomes failed to survive. Females without a single copy of the microRNA developed normally. 

The findings showed that having one intact copy of the microRNA is essential for male survival. Without it, key genes on the Z chromosome became overly active, disrupting development. 

The same microRNA was found in all bird species studied, but not in other animals. It is the only known microRNA essential for the survival of just one sex.

The team’s study also reveals how the imbalance problem arose. When female birds lost genes on the W chromosome, the activity of certain genes on the Z chromosome was increased to compensate. 

But in males, who have two Z chromosomes, this led to too much activity. 

Birds solved this with a clever trick – they use the microRNA to turn down these genes, but only in males. 

This biological process is very different from the way that mammals – which have males with XY chromosomes and females with XX – are known to resolve the same issue. 

The study shows that birds evolved their own unique way to balance gene activity between the sexes.

The research, published in Nature, was carried out in collaboration with the National Avian Research Facility. It was supported by the European Research Council, the Swedish Research Council (VR and Formas), and the UK Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation.